Substance abuse is a major public health problem that is on the rise among adolescent girls. Despite this, we know relatively little about what risk factors lead to substance use and abuse in girls. One important risk factor that is significant for girls and that show changes in adolescence is the family environment. Previous research indicates that a family history of addiction and poor reported parenting are linked to youth's substance use, particularly for girls. However, how poor global parenting leads to substance abuse risk is not known. In addition, although talking with children about drug use is widely recommended to parents, the specific parental advice about drug use that is most effective is not known. The proposed study will address this knowledge gap by using an innovative, newly developed, and validated laboratory paradigm to assess observed parenting behaviors and adolescent multi-modal emotional and physiological responses to parent- adolescent conflict and drug use discussion interactions as these predict increases in adolescent substance use from early to middle adolescence. We hypothesize that observed parenting behaviors in the conflict and drug use discussion interactions (e.g., low warmth, high criticism, avoidance of drug discussion) and heightened adolescent emotional and physiological responses will predict initiation of and increases in substance use/abuse over time and that this prediction will be stronger for girls than boys. We will observe parent-adolescent interactions in a representative community sample of 240 12-13 year old girls and boys. In a laboratory session, parent-adolescent pairs will discuss a personalized conflict topic and the topic of drug use. Parenting behaviors (warmth, structuring, and criticism) and content of drug use discussions (avoiding drug discussion, discussing rules, examples, and consequences of drug use) and contingent emotion and heart rate will be coded continuously using a novel micro-analytic coding system. Before and at repeated time-points during and after the interaction, adolescents' and parents' emotional, physiological (heart rate, blood pressure), and neuroendocrine (cortisol) arousal will be assessed. Youth will complete biological, self-report, and clinical interview measures of substance use and abuse and associated behavior problems and depressive symptoms at Time 1 and at 6 month, and 1, 2, and 3 year follow ups. Parents will complete clinical interviews of their substance abuse and stress. Hypotheses will be tested with sophisticated longitudinal modeling techniques including Hierarchical Linear Modeling (HLM). If the hypotheses are supported, the proposed study will isolate targets for gender-based prevention programs, addressing NIDA's mission of identifying risk factors to improve intervention efficacy. Family-based preventions could identify girls with high responses to brief family talks and could target specific parenting behaviors and parent drug use advice that reduces youth arousal and substance use. Through this work we hope to discover novel, gender-sensitive, prevention strategies.